PMID- 33166450 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20210211 LR - 20210211 IS - 1520-5126 (Electronic) IS - 0002-7863 (Print) IS - 0002-7863 (Linking) VI - 142 IP - 46 DP - 2020 Nov 18 TI - Impact of Multiple Hydrogen Bonds with Fluoride on Catalysis: Insight from NMR Spectroscopy. PG - 19731-19744 LID - 10.1021/jacs.0c09832 [doi] AB - Hydrogen-bonding interactions have been explored in catalysis, enabling complex chemical reactions. Recently, enantioselective nucleophilic fluorination with metal alkali fluoride has been accomplished with BINAM-derived bisurea catalysts, presenting up to four NH hydrogen-bond donors (HBDs) for fluoride. These catalysts bring insoluble CsF and KF into solution, control fluoride nucleophilicity, and provide a chiral microenvironment for enantioselective fluoride delivery to the electrophile. These attributes encouraged a (1)H/(19)F NMR study to gain information on hydrogen-bonding networks with fluoride in solution, as well as how these arrangements impact the efficiency of catalytic nucleophilic fluorination. Herein, NMR experiments enabled the determination of the number and magnitude of HB contacts to fluoride for thirteen bisurea catalysts. These data supplemented by diagnostic coupling constants (1h)J(NH...F(-)) give insight into how multiple H bonds to fluoride influence reaction performance. In dichloromethane (DCM-d(2)), nonalkylated BINAM-derived bisurea catalyst engages two of its four NH groups in hydrogen bonding with fluoride, an arrangement that allows effective phase-transfer capability but low control over enantioselectivity for fluoride delivery. The more efficient N-alkylated BINAM-derived bisurea catalysts undergo urea isomerization upon fluoride binding and form dynamically rigid trifurcated hydrogen-bonded fluoride complexes that are structurally similar to their conformation in the solid state. Insight into how the countercation influences fluoride complexation is provided based on NMR data characterizing the species formed in DCM-d(2) when reacting a bisurea catalyst with tetra-n-butylammonium fluoride (TBAF) or CsF. Structure-activity analysis reveals that the three hydrogen-bond contacts with fluoride are not equal in terms of their contribution to catalyst efficacy, suggesting that tuning individual electronic environment is a viable approach to control phase-transfer ability and enantioselectivity. FAU - Ibba, Francesco AU - Ibba F AUID- ORCID: 0000-0002-2739-4156 AD - Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford OX1 3TA, United Kingdom. FAU - Pupo, Gabriele AU - Pupo G AUID- ORCID: 0000-0003-3084-3888 AD - Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford OX1 3TA, United Kingdom. FAU - Thompson, Amber L AU - Thompson AL AD - Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford OX1 3TA, United Kingdom. FAU - Brown, John M AU - Brown JM AD - Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford OX1 3TA, United Kingdom. FAU - Claridge, Timothy D W AU - Claridge TDW AUID- ORCID: 0000-0001-5583-6460 AD - Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford OX1 3TA, United Kingdom. FAU - Gouverneur, Veronique AU - Gouverneur V AUID- ORCID: 0000-0001-8638-5308 AD - Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford OX1 3TA, United Kingdom. LA - eng PT - Journal Article DEP - 20201109 PL - United States TA - J Am Chem Soc JT - Journal of the American Chemical Society JID - 7503056 SB - IM PMC - PMC7677927 COIS- The authors declare no competing financial interest. EDAT- 2020/11/10 06:00 MHDA- 2020/11/10 06:01 PMCR- 2020/11/20 CRDT- 2020/11/09 20:12 PHST- 2020/11/10 06:00 [pubmed] PHST- 2020/11/10 06:01 [medline] PHST- 2020/11/09 20:12 [entrez] PHST- 2020/11/20 00:00 [pmc-release] AID - 10.1021/jacs.0c09832 [doi] PST - ppublish SO - J Am Chem Soc. 2020 Nov 18;142(46):19731-19744. doi: 10.1021/jacs.0c09832. Epub 2020 Nov 9.